Regional Release and Clearance of C-Type Natriuretic Peptides in the Human Circulation and Relation to Cardiac Function
Regional Release and Clearance of C-Type Natriuretic Peptides in the Human Circulation and Relation to Cardiac Function
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DOI：
10.1161/hypertensionaha.109.135608
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发表时间：
2009-09-01
期刊：
影响因子：
8.3
通讯作者：
Richards, A. Mark
中科院分区：
文献类型：
--
作者：
Palmer, Suetonia C.;Prickett, Timothy C. R.;Richards, A. Mark
血浆c型利钠肽（CNP）的产生和清除以及氨基末端(NT)-proCNP的免疫反应性在人体循环中的特征仍然很差。因此，我们测量了120名心血管疾病研究对象（年龄：64.2 +/- 9.0岁；73%为男性）心导管插入期间多个组织床上CNP和NT-proCNP的动脉和静脉浓度。心脏、头颈部和肌肉骨骼组织对血浆CNP和NT-proCNP的贡献最明显（P < 0.05）。肝组织中NT-proCNP也有净释放（P < 0.001）。在肾、肝和肺组织中观察到CNP的阴性动静脉梯度（P < 0.05），表明净清除，而未发现NT-proCNP清除的组织特异性位点。在多变量分析中，年龄、平均肺动脉压、左室舒张末压、心肌危险的Brandt评分和肌钙蛋白I是循环CNP水平的独立预测因子。性别和肾功能是动脉NT-proCNP的独立预测因素。CNP在整个心脏的比例上升（+60%）小于脑利钠肽（+123%），但大于nt -原脑利钠肽（NT-proBNP）（+36%）和NT-proCNP（+42%，所有P < 0.001）。我们得出结论，心脏和头颈部组织是CNP的重要来源。循环CNP浓度与心脏血流动力学负荷和缺血负荷相关，而与NT-proCNP浓度无关。虽然心脏释放是最明显的，但许多其他组织释放NT-proCNP的免疫反应性，没有证据表明NT-proCNP降解的器官特异性位点。综上所述，与NT-proCNP相比，CNP在跨器官梯度的大小和方向上的差异表明，净全面性共分泌具有不同的清除机制。(高血压。2009;54:612 - 618)。
Production and clearance of plasma C-type natriuretic peptide (CNP) and amino terminal (NT)-proCNP immunoreactivity in the human circulation remain poorly characterized. Accordingly, we have measured arterial and venous concentrations of CNP and NT-proCNP across multiple tissue beds during cardiac catheterization in 120 subjects (age: 64.2 +/- 9.0 years; 73% men) investigated for cardiovascular disorders. The heart, head and neck, and musculoskeletal tissues made the clearest contributions to both plasma CNP and NT-proCNP (P < 0.05). Net release of NT-proCNP was also observed from hepatic tissue (P < 0.001). Negative arteriovenous gradients for CNP were observed across renal, hepatic, and pulmonary tissue (P < 0.05), indicating net clearance, whereas no tissue-specific site of NT-proCNP clearance was identified. Age, mean pulmonary artery pressure, left ventricular end diastolic pressure, Brandt score of myocardial jeopardy, and troponin I were independent predictors of circulating CNP levels in multivariable analysis. Sex and kidney function were independently predictive of arterial NT-proCNP. The proportional step-up of CNP (+60%) across the heart was less than for brain natriuretic peptide (+123%) but greater than for NT-pro-brain natriuretic peptide (NT-proBNP) (+36%) and NT-proCNP (+42%; P < 0.001 for all). We conclude that cardiac and head and neck tissue are important sources of CNP. Circulating CNP but not NT-proCNP concentrations are related to cardiac hemodynamic load and ischemic burden. Although cardiac release is most evident, multiple additional tissues release NT-proCNP immunoreactivity without evidence for an organ-specific site for NT-proCNP degradation. Taken together, differences in magnitude and direction of transorgan gradients for CNP compared with NT-proCNP suggest net generalized cosecretion with differing mechanisms of clearance. (Hypertension. 2009;54:612-618.)